Regulation of the ovarian function through the Hippo pathway

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09798
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: University of Fukui
• Principal Investigator: Mizutani Tetsuya 福井大学, 学術研究院医学系部門, 准教授 (90322734)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 卵巣 / 顆粒膜細胞 / ステロイドホルモン / YAP / TAZ

Outline of Final Research Achievements

Hippo pathway is an evolutionarily conserved signaling pathway that controls organ size by phosphorylating and inhibiting the transcription co-activators YAP/TAZ in mammals. To elucidate the role of YAP/TAZ in ovarian granulosa cells, the gain-of-function (using the constitutively active mutant) and the loss-of-function analyses (using the siRNA) of YAP/TAZ were performed. Gene expression of steroidogenic enzymes, CYP19A1, CYP11A1 and HSD3B2, were down-regulated by YAP/TAZ. Furthermore, the transcription factor TEAD is involved in YAP/TAZ-mediated these gene expressions. These results suggest that the YAP/TAZ-TEAD nuclear complex is novel negative regulator of steroidogenesis in ovarian granulosa cells.

Free Research Field

生殖内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究により、新たなステロイドホルモン産生メカニズムが解明された。
これにより未だ不明なステロイドホルモン産生疾患の解明につながる可能性が示された。また、将来的に本研究から新しいステロイドホルモン産生疾患に対する治療法が開発されることが期待される。